Int J Clin Exp Med 2015;8(4):5085-5093 www.ijcem.com /ISSN:1940-5901/IJCEM0005230

Original Article Ultrasound findings of mild neonatal periventricular-intraventricular hemorrhage after different treatments Sida Wang1, Chunyan Liao1, Shuyuan Liang1, Danni Zhong2, Junjie Liu1, Zhixian Li1 Departments of 1Diagnostic Ultrasound, 2Neonatology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China Received December 25, 2014; Accepted March 26, 2015; Epub April 15, 2015; Published April 30, 2015 Abstract: Objective: To investigate the ultrasound findings of mild neonatal periventricular-intraventricular hemorrhage (PIVH) after different treatments, and to evaluate the neurological outcomes of mild PIVH with Gesell Development Diagnosis Scale (GDDS). Methods: A total of 194 newborns with grade I-II PIVH were recruited, and findings of cranial ultrasound examination before and 1 month after birth were included for analysis. The echo intensity and size of the lesions were recorded. Results: There was no significant difference in the echo intensity among three groups of grade I PIVH patients (P>0.05). There was significant difference in the echo intensity among three groups of grade II PIVH patients, and the ganglioside had the best therapeutic efficacy (P0.05). However, significant difference was observed in the area change among three groups of grade II PIVH patients, and ganglioside had a better efficacy than cerebrolysin and control agent (P0.05). GDDS evaluation showed no significant difference among three groups (P>0.05), and all the patients recovered completely. Conclusion: The efficacy of different treatments for mild PIVH can be reflected in the ultrasound findings. Mild PIVH children generally have a good neurological prognosis. Keywords: Periventricular-intraventricular hemorrhage, Gesell Development Diagnosis Scale, neonatal, ultrasound

Introduction Periventricular-intraventricular hemorrhage (PIVH) has the highest incidence among neonatal intracranial hemorrhagic diseases, and severe hemorrhage usually results in adverse neurodevelopment [1, 2]. There are a variety of methods used to detect the neonatal cranial lesions, such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography [3, 4]. With the development of neonatal cranial ultrasound technology, cranial ultrasound has become an important means in screening PIVH in newborns. Ultrasound has many advantages such as convenience, dynamic observation and no radiation. It has a high sensitivity in the diagnosis of subependymal hemorrhage and intraventricular hemorrhage [5-7]. At present, neonatal PIVH requires a comprehensive treatment. Gangliosides belong to a class of sialic acid-containing glycosphingolipid that is widely

present in the cell membrane of vertebrates, especially in the brain of fetus and newborn infants. Ganglioside therefore plays a crucial role in the neuronal differentiation, neurite outgrowth, and synapse formation [8, 9]. Some studies have shown that ganglioside is the only nerve glycosides that can pass through the blood brain barrier (BBB) [9]. In recent years, its therapeutic effect on neonatal hypoxic-ischemic encephalopathy has been reported in clinical practice and animal studies [10, 11], but its effect on neonatal PIVH is less reported. Due to the progression of diagnostic imaging methods, the clinical diagnosis rate of PIVH is increasing. The symptoms of neonatal PIVH are various, and it was reported that about 25%-50% PIVH children were not diagnosed due to absence of evident symptoms. Recently, long-term followup and investigations have pointed out that PIVH children have risk for cerebral palsy, mental retardation and other significant adverse

Ultrasound in mild neonatal periventricular-intraventricular Table 1. General information of children in three groups Item Gestational age (weeks) Birth weight (g) Asphyxia degree (n, %) Mild Severe

Control group (n=63) Ganglioside group (n=60) Cerebrolysin group (n=71) P value 35.8 ± 3.9 36.6 ± 2.5 37.1 ± 3.2 0.342 2915.2 ± 883.6 2915.2 ± 883.6 2778.6 ± 689.6 0.968 43, 68.3% 20, 31.7%

outcomes in school age and adolescence, even they have mild PIVH [12]. Thus, some investigators concern about whether PIVH affects the children’s intellectual development. Currently, there are a variety of methods used to evaluate the intellectual development of children, such as the Wechsler scale, Raven’s Standard Progressive Matrices, Bayley Scales of Infant Development, and Gesell Development Diagnosis Scale (GDDS). In the present study, the ultrasound findings of grade I-II PIVH before and after different treatments were evaluated, and GDDS scores were employed for the assessment of therapeutic outcomes. Materials and methods General information Patients who were hospitalized in the Department of Neonatology of the First Affiliated Hospital of Guangxi Medical University between May 2012 and August 2014 were recruited into present study. Inclusion criteria: asphyxia of varying degrees, initial cranial ultrasound examination within 7 days after birth, cranial ultrasound examination showing grade I-II PIVH (mild PIVH, Papile’s classification), a second cranial ultrasound examination performed after therapy and GDDS available at 1 month after birth. Exclusion criteria: Concomitant primary diseases. A total of 194 newborns (105 boys, 89 girls) with a total of 350 lesions were included for final analysis. The gestational age at birth, birth weight and asphyxia degree were recorded. In this study, gestational age at birth was 28 to 41 weeks (mean: 36 ± 3 weeks). There were 58 preterm children and 101 full-term children. The birth weight was 1100-4190 g (average: 2768.1 ± 790.8 g). There were 65 low birth weight children and 129 normal birth weight children. A total of 133 children had mild asphyxia and 61 had severe asphyxia. There were no significant differences in the gestational age, birth weight and asphyxia degree among three groups

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42, 70% 18, 30%

48, 67.6% 23, 32.4%

0.075 0.067

(P>0.05, Table 1). The effects of different treatments were comparable in the present study. Diagnostic criteria PIVH neonate were classified into grade I-II according to the Papile’s classification [13]: Grade I: subependymal (germinal matrix) hemorrhage; Grade II: Hemorrhage extending to the ventricular system and occupying Cerebrolysin group > Control group.

Table 5. GDDS score of different treatment groups Control group (n=63) Adaptability 86.69 ± 15.77 Gross motor movement 89.07 ± 13.07 Fine movement 90.57 ± 12.39 Social contact 90.97 ± 11.87 Score

Ganglioside group (n=60) 86.50 ± 14.27 90.39 ± 12.01 89.63 ± 13.58 89.91 ± 12.55

Cerebrolysin P value group (n=71) 87.42 ± 16.88 0.706 91.68 ± 12.55 0.518 90.63 ± 15.76 0.712 88.13 ± 11.26 0.405

ge of PIVH occurred within 1-3 days after birth; more than 90% of PIVH could be identified within 4-5 days after birth. In this study, the initial ultrasound examination was done one week after birth, when the incidence newborn PIVH is high, and the lesions can be clearly identified.

Grade I PIVH is originated from the germinal matrix, especially in preterm neonates. Footnotes: The differences of the GDDS score in the three groups were not statistically signifiThe germinal matrix cant. is present in 24-32 weeks fetus. It is an vation and bedside application, cranial ultraimmature thin-walled capillary network locating sound has become a non-substitutable tool for in the thalamic-caudate groove between cauthe detection of neonatal intracranial lesions. date nucleus and thalamus. Approximately 30-55% of germinal matrix hemorrhage occurs Currently, neonatal PIVH treatment required a in newborns less than 32 weeks in gestational comprehensive treatment which is still controage or lower than 1500 g in birth weight [7]. versial, especially in mild PIVH. The supportive This subependymal hemorrhagic remain isolattreatments include oxygen supply, maintenaed or may expand into the lateral ventricle. Ultrance of blood glucose, use of hemostatic agents, sonography shows focal hyperechoic area loincreasing intracranial pressure, and reducing cating in the thalamic-caudate groove between movement. The treatment also includes the caudate nucleus and thalamus. When the subuse of cerebrolysin and citicoline to protect ependymal hemorrhage begins to absorb, brain cells, as well involves the introduction of ultrasonography shows focal hypoechoic area the special nerve growth factor like ganglioside, or echoless area surrounding by hyperechoic which plays a key role in repairing damaged line. Large hemorrhage may narrow and deform central nervous system. In addition, there are the anterior horn lateral ventricular. Neonates invasive treatments such as puncture and surwith isolated grade I PIVH generally have no gery. This study was to investigate the ultraobvious clinical symptoms or abnormal perinasound findings of PIVH after different treattal history. This hemorrhage has relatively good ments. The therapeutic effect of ganglioside on prognosis and no significant neurological the neonatal hypoxic-ischemic encephalopathy sequelae. has been reported in previous studies, but its efficacy on neonatal PIVH is less studied. As an Grade II PIVH might be isolated or developed imported drug in China, ganglioside is relatively from grade I PIVH. Ultrasonography shows focal expensive and currently has prudent applicahyperechoic area, located in the choroid plexus tion in clinical practice. However, for mild PIVH, triangular, which may occupy partially or comto our knowledge, the prognosis is usually good, pletely the entire lateral ventricle. Ultrasonoand whether special pharmacotherapy is needgraphy also shows significant thickening (usued remains controversial. ally >1.20 cm), extension or surface roughness of the choroid plexus. Neurological outcome is In this study, ultrasound was employed for the generally good. detection of neonatal PIVH. Wen et al [17] found that the incidence of PIVH in high risk The natural absorption, liquefaction and formainfants was 92% in utero, intrapartum or 1 day tion of grade I PIVH cysts usually take about 2-3 after birth, and the remaining percentaweeks. In the present study, the changes in 5091

Int J Clin Exp Med 2015;8(4):5085-5093

Ultrasound in mild neonatal periventricular-intraventricular echo intensity and size of lesions in each treatment group, and there was no significant difference among each group for grade I PIVH patients (P>0.05). This means that, for the mild PIVH, general supportive therapy in the liquefaction and absorption periods is sufficient. However, the absorption period of grade II PIVH is generally longer. Fresh hemorrhagic lesions appear hyperechoic, and reduction in echo intensity means that the lesions are entering the absorption and remission stage. In this study, the changes in echo intensity were compared among patients with grade II lesions. Results showed that ganglioside had the best therapeutic efficacy, followed by cerebrolysin therapy and support treatment (P0.05). Kang et al [18] investigated 22 PIVH premature infants treated with ganglioside by neonatal behavioral neurological assessment, and found that ganglioside could improve the neurological behaviors and neuromotor symptoms of PIVH. The sample size of Kang’s study was small as in our study. The effect of ganglioside on the neurological outcomes still is needed to confirm in more clinical investigations with large sample size and longer follow-up period. There are several issues in this study that need further exploration. Firstly, unlike in CT and MRI, standard sections of ultrasonography are usually controlled manually, and thus it is not easy to control the accuracy of measurement. Although there are relatively standard sections for ultrasonography, the detection is easier to be affected by human factors to some extents. 5092

The determination of echo intensity and lesion size varies among investigators. In the present study, a number of methods were employed for quality control: a doctor with rich experience in ultrasound examination performed ultrasonography, and the determination of echo intensity and measurement of lesion size had relatively uniform standards; the largest section of the lesions was used for assessments and measurements, and three measurements were done for averages; the ultrasound images were two-dimensional, but the hemorrhagic lesions were three-dimensional, which might make the lesion size measurements incomplete. In clinical application, three-dimensional ultrasound can be considered for accurate assessments and measurements. Conclusion The efficacy of different treatments for mild PIVH can be reflected by ultrasound findings. Mild PIVH children generally have a good neurological prognosis. Acknowledgements This study was supported by the Guangxi Natural Science Foundation Program, China (No. 2012GXNSFAA239002) and Guangxi Program on Key Health Research Project of China (No. Key 2012074). Disclosure of conflict of interest None. Address correspondence to: Zhixian Li, Department of Diagnostic Ultrasound, First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530021, Guangxi, China. Tel: +86771-5356706; E-mail: [email protected]

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Int J Clin Exp Med 2015;8(4):5085-5093

Ultrasound findings of mild neonatal periventricular-intraventricular hemorrhage after different treatments.

To investigate the ultrasound findings of mild neonatal periventricular-intraventricular hemorrhage (PIVH) after different treatments, and to evaluate...
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